Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors

J Neurochem. 2011 Apr;117(2):333-45. doi: 10.1111/j.1471-4159.2011.07208.x. Epub 2011 Feb 25.


We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, the blood-brain barrier (BBB). Brain microvessels were isolated from brain cortexes of seven males (16-77 years old) and protein expression of 114 membrane proteins was determined by means of a liquid chromatography-tandem mass spectrometric quantification method using recently established in-silico peptide selection criteria. Among drug transporters, breast cancer resistance protein showed the most abundant protein expression (8.14 fmol/μg protein), and its expression level was 1.85-fold greater in humans than in mice. By contrast, the expression level of P-glycoprotein in humans (6.06 fmol/μg protein) was 2.33-fold smaller than that of mdr1a in mice. The organic anion transporters reported in rodent BBB, that is, multidrug resistance-associated protein, organic anion transporter and organic anion-transporting polypeptide family members, were under limit of quantification in humans, except multidrug resistance-associated protein 4 (0.195 fmol/μg protein). Among detected transporters and receptors for endogenous substances, the glucose transporter 1 level was similar to that of mouse, while the L-type amino acid transporter 1 level was fivefold smaller than that of mouse. These findings should be useful for understanding human BBB function and its differences from that in mouse.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Animals
  • Biological Transport / physiology
  • Blood-Brain Barrier / metabolism*
  • Brain / cytology
  • Chromatography, Liquid / methods
  • Humans
  • Male
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Middle Aged
  • Proteomics / methods*
  • Receptors, Cell Surface / metabolism*
  • Tandem Mass Spectrometry / methods
  • Young Adult


  • Membrane Proteins
  • Membrane Transport Proteins
  • Receptors, Cell Surface